Organ donation: when should we consider intestinal donation

ORIGINAL ARTICLE

Organ donation: when should we consider intestinaldonationCarl-Ludwig Fischer-Frohlich,1 Alfred Konigsrainer,2 Randolph Schaffer,3 Franz Schaub,4

Johann Pratschke,5 Andreas Pascher,6 Wolfgang Steurer7 and Silvio Nadalin2

1 Region Baden-Wurttemberg, Deutsche Stiftung Organtransplantation, Stuttgart, Germany

2 Klinik fur Allgemein, Viszeral- und Transplantationschirurgie, Universitatsklinikum Tubingen, Tubingen, Germany

3 Scripps Center for Organ and Cell Transplantation, Scripps Clinic Medical Group, La Jolla, CA, USA

4 Deutsche Stiftung Organtransplantation, Frankfurt, Germany

5 Universitatsklinik fur Visceral-, Transplantation- und Thoraxchirurgie, Innsbruck, Austria

6 Charite, Campus Virchow-Klinikum, Klinik fur Allgemein-, Visceral- und Transplantationschirurgie, Berlin, Germany

7 Abteilung fur Allgemein- und Viszeralchirurgie Robert-Bosch-Krankenhaus, Auerbachstraße Stuttgart, Germany

Introduction

Intestinal transplantation (IT) in the form of isolated

intestinal (IIT) or multivisceral transplantation (MVT)

represents nowadays a clinical reality utilized for many

indications with more than 50% of the recipients being

children [1–3]. Between 2000 and 2011, 74 ITs have been

performed in Germany at 10 centres.

Although more than 2300 ITs have been performed

worldwide, the field of transplantation still lacks a

description of intestinal donor criteria. Only single-centre

experiences and personal communications have been

reported until now [2,4–13]. A simple definition of

‘inclusion-criteria’ to be considered during donor evalua-

tion would be an indispensable tool for all members of

the medical community involved: coordinators, organ

procurement organizations (OPO), physicians at the

intensive care unit (ICU) and transplant surgeons.

The aim of our study was to address this deficiency

through a retrospective analysis of donor-evaluation of 39

deceased ITT/MVT donors in Germany whose organs

were successfully transplanted during the last 6 years and

Keywords

deceased donor, intestinal donor profile,

intestinal transplantation, multivisceral

transplantation, small bowel transplantation.

Correspondence

Silvio Nadalin MD, Klinik fur Allgemein,

Viszeral- und Transplantationschirurgie,

Universitatsklinikum Tubingen, Hoppe Seyler

Str 3, 72076 Tubingen, Germany.

Tel.: +49 7071 2986600;

fax: +49 7071 294934;

e-mail: [email protected]

Conflicts of Interest

The authors disclose no commercial associa-

tion that may pose a conflict of interest in

connection with the submitted manuscript.

Received: 7 March 2012

Revision requested: 3 May 2012

Accepted: 8 August 2012

Published online: 21 September 2012

doi:10.1111/j.1432-2277.2012.01556.x

Summary

Although more than 2300 intestinal transplantations (IT) have been performed

worldwide, a description of intestinal donor criteria is still missing. This causes

confusion among transplant coordinators, OPOs, physicians at intensive care

unit and transplant surgeons. A Med-line search looking for publications about

donor criteria or donor selection in human IT was performed in December

2011. Retrospective analysis of 39 deceased donors from whom, in the period

January 2006–December 2011, 20 isolated intestinal grafts and 19 multivisceral

grafts were recovered and successfully transplanted. Review of the Literature:

Among 3504 publications about IT, no study reported specifically about intesti-

nal donor profile. The most commonly cited donor criterion was age, while all

other criteria were inconsistently discussed. Based on the collected data, we

suggest following inclusion criteria for donation of IT grafts: age 0–50 years,

ICU-stay <1 week, no blunt abdominal trauma, most recent Sodium

<155 mmol/l, no severe ongoing transfusion requirements, standard donor

therapy including early enteral nutrition and a compatible donor–recipient size

match. By providing simple criteria for intestinal donation from deceased

donor, we may help to properly utilize the limited donor pool.

Transplant International ISSN 0934-0874

ª 2012 The Authors

Transplant International ª 2012 European Society for Organ Transplantation 25 (2012) 1229–1240 1229

to compare these results with the ones reported interna-

tionally through a systematic review of the literature.

Patients and methods

Review of the literature

Med-line search using the key-words ‘intestinal’, ‘trans-

plantation’, ‘small bowel’, ‘donor’, ‘criteria’, ‘selection’,

was performed in December 2011. Publications about IT

in humans were reviewed for investigating donor criteria

or donor selection.

Personal experience

We performed a retrospective analysis of 39 deceased

donors from whom, in Germany, in the period January

2006–December 2011, 20 isolated intestinal (II) grafts and

19 multivisceral (MV) grafts were recovered and success-

fully transplanted. II grafts were defined as including the

small bowel with or without a colon-segment; while MV

grafts included the II graft with other abdominal organs

(e.g. intestine + liver (en bloc or separated) or intes-

tine + liver + pancreas + stomach + duodenum en bloc

or intestine + pancreas + stomach + duodenum en bloc).

Data were extracted from the anonymized database of

the German OPO–Deutsche Stiftung Organtransplanta-

tion (DSO)–according to the donor information form as

suggested by the European Committee of Experts on

Organ Transplantation [14]. Data were analysed for every

donor including recipient demographics and initial graft

function (at 30 days and 1 year).

Continuous variables were presented as median and

range (minimum–maximum) and ordinal variables as

absolute number and percentage. Graft function rates

were calculated according to the Kaplan–Maier method.

Results

Review of the literature

Among 3504 publications about IT (keywords ‘intestine’

‘donor’), only 32 reported about human IT matching the

keywords ‘intestinal’, ‘transplantation’, ‘donor’, ‘criteria’,

‘selection’ and ‘small bowel’.

There was no detailed study specifically aimed at defin-

ing an intestinal donor profile. The intestinal donor crite-

ria extracted from our analysis of the international

literature are outlined in Table 1.

Only 4 centres reported about their own large series

(i.e. Pittsburgh n = 500, Miami n = 141, Washington

n = 67 and Indianapolis n = 57) and mentioned about

donor issue in different kinds of recipients [4, 9, 11, 27,

41–44].

The Pittsburgh group reported for the first time in

1997 about donor’s risk factors affecting the early out-

come in 72 patients who received 77 intestinal grafts.

They showed that high vasopressor, prolonged cold

ischaemia time, and high sodium affected the early graft

survival and intestinal graft injury [42]. This was the first

paper correlating donor data with outcome. As the same

group in 2009 reported about 500 cases of intestinal and

MVT, the only donor’s variables reported but not further

discussed were a young age (mean age of 16.6 years) and

ABO-blood type identity.

In the Miami series with 141 paediatric intestinal and

MVT, only the following donor’s parameters were

described, but nowhere discussed or correlated with out-

come (neither early nor late) : a median donor age of

1.67 years, a median donor/recipient body weight ratio

range of 1.04. HLA match was not considered a relevant

factor [9].

The Washington group analysed their own series of 67

ITs and compared the outcome of 12 grafts from donors

who underwent cardiopulmonary resuscitation versus 55

who did not. The authors concluded that a donor history

of cardiac arrest and consequent CPR should not auto-

matically exclude the use of the intestine graft for trans-

plantation [11].

The Group from Indianapolis analysed the outcome of

IT and MVT in correlation with the solution used to per-

fuse the grafts (i.e. UW-Solution in 22 vs. HTK-Solution

in 35 cases). The authors showed no difference in patient

and graft survival at POD 30 and POD 90 after transplan-

tation. Additionally, no differences was noted in initial

function, endoscopic appearance, rejection episodes or

transplant pancreatitis in case of MVT [27].

In summary, the various reports of individual donor

series revealed a total of 8 different donor criteria [i.e. (i)

age, (ii) body weight or donor/recipient body weight

ratio, (iii) ICU-stay, (iv) cause of death, (v) cardiac arrest

or CPR, (vi) hypernatraemia, (vii) blood group identity

and (viii) HLA-match). No more than 4 criteria were

considered in any single report. The most commonly

cited donor criterion was age, while all other criteria were

inconsistently discussed.

Personal experience

Detailed donor data are reported in Table 2. All donors

(15 male and 24 female) were heart-beating brain-dead

deceased donors. The median age was 21 years.

(8 months–51 years.), height 170 cm (78–195), weight

63 kg (11–85) and body mass index (BMI) 21 kg/m2 (14–

25). Most of the recipients (90%) were older than

18 years of age.

Intestinal donor profile Fischer-Frohlich et al.

ª 2012 The Authors

1230 Transplant International ª 2012 European Society for Organ Transplantation 25 (2012) 1229–1240

Tab

le1.

Rev

iew

of

the

liter

ature

conta

inin

gsp

ecifi

cdat

aab

out

donor

incl

usi

on

criter

iafo

rin

test

inal

pro

cure

men

t.

Donor

age

Size

mat

chIC

U-s

tay

Cau

seof

dea

th

Vas

opre

ssors

,ca

rdia

c

arre

stLa

bora

tory

par

amet

ers

Oth

erfindin

gs

§To

do

etal

.[4

4]

1994

Donor

criter

iaeq

uiv

alen

t

toliv

erdonor

in1994

§Fu

ruka

wa

etal

.

[42]

1997

and

Cas

avill

a

etal

.[4

1]

1993,

(n=

77)

range

0–4

8ye

ars

NR

range

1–2

1day

sN

RH

igh-d

ose

vaso

pre

ssor

atre

cove

rydet

rim

enta

l,

no

com

men

ton

card

iac

resu

scitat

ion

(10

of

77

case

s)

hyp

ernat

raem

ia

det

rim

enta

l

pro

longed

isch

aem

ia

tim

esdet

rim

enta

l

§A

bu-E

lmag

det

al.

[43]

2001,

(n=

165)

All

AB0

iden

tica

lex

cept

1:

HLA

-mat

chat

random

;C

MV

D+

acce

pte

din

MV

Tor

Live

r-IT

§A

bu-E

lmag

det

al.

[4]

2009,

larg

est

single

-cen

tre

report

of

IIT/M

VT

(n=

500)

16.6

±13.6

year

s

(ran

ge

0.0

1–5

4

year

s)

NR

NR

NR

NR

NR

6A

B0

com

pat

ible

,494

AB0

iden

tica

l440

UW

,

60

HTK

:w

ith

HTK

risk

for

gra

ftpan

crea

titis

in

MV

T

Farm

er[6

]2008

13.3

±8.4

year

sdonor

<re

cipie

nt

wei

ght

ratio:

(0.9

5±

0.5

)

NR

NR

no

signifi

cant

dow

n-t

ime,

card

iac

arre

st,

inotr

opic

support

NR

NR

Gondole

siet

al.

[7]

2008

(rev

iew

of

oth

erst

udie

s)

NR

donor

50–7

5%

of

reci

pie

nt

NR

NR

DC

Dnot

pre

ferr

edN

RN

R

Jan,

Ren

z[8

]2005

(rev

iew

of

oth

erst

udie

s)

NR

donor

<50–7

5%

of

reci

pie

nt

NR

NR

NR

NR

pro

cure

men

tqual

ity

import

ant

Kat

oet

al.

[9]

2006,

IIT/

MV

Tin

child

ren

(n=

141)

range

0–5

9ye

ars

donor

wei

ght:

11

(2.7

–67)

kg

NR

NR

NR

NR

Gra

ftsi

zere

duct

ion

and

AB0

com

pat

ible

IIT/M

VT

for

ove

rcom

ing

mis

mat

ch;

HLA

-mat

chat

random

;C

MV

D+

acce

pte

d

Man

gus

etal

.[2

7]

2008

:

UW

(n=

22)

vs.

HTK

(n=

35)

0–1

8ye

ars

n=

41,

>18

year

sn

=16

donor

wei

ght

<25

kgn

=16

NR

60%

trau

mat

icN

RN

RN

odiffe

rence

in

outc

om

e;no

pan

crea

titis

inM

VT

with

HTK

or

UW

Mat

sum

oto

etal

.[1

1]

2008:

donors

with

CPR

(n=

12)

vs.

donors

without

CPR

(n=

55)

CPR

:7.7

±12.6

year

s

(6w

eeks

–44

year

s)

without

CPR

:

10.4

±12.7

year

s

NR

CPR

115

±62

hrs

(>1

wee

k)w

ithout

CPR

97

±86

h

CPR

:50%

hyp

oxi

a

without

CPR

:75%

trau

mat

ic

CPR

19

±13

(1–5

2)

min

CPR

:N

a146

±12*,

term

inal

ASA

T/A

LAT

<100‡

without

CPR

:

Na

144

±10*l

2nonsu

rviv

ors

with

15/2

5m

inC

PRan

dIC

U

stay

55/1

6h

Fischer-Frohlich et al. Intestinal donor profile

ª 2012 The Authors


Tab

le1.

continued

Donor

age

Size

mat

chIC

U-s

tay

Cau

seof

dea

th

Vas

opre

ssors

,ca

rdia

c

arre

stLa

bora

tory

par

amet

ers

Oth

erfindin

gs

Maz

arie

gos

etal

.[3

4]

2010:

real

ized

IIT/M

VT

donors

,(n

=1347,

1998–2

008,

USA

)

0–5

0ye

ars

NR

NR

NR

<3

vaso

pre

ssors

atcr

oss

-cla

mp,

CPR

<15

min

afte

rbra

in

dea

th,

no

DC

D

Na

<170*,

ASA

T/A

LAT

<500‡,

Cre

atin

ine

<2†

NR

Nie

uw

enhuijs

etal

.[1

2]

2008

(rev

iew

of

oth

erst

udie

s)

<50

year

sdonor

<re

cipie

nt

NR

NR

No

pro

longed

hae

modyn

amic

inst

abili

ty,

no-m

inim

al

inotr

opic

support

NR

Bra

indea

thca

use

sSI

RS

and

org

andys

funct

ion:

requires

donor

ther

apy

Plat

z,M

uel

ler

[45]

2005,

(n=

14)

<50

year

sdonor

BM

I

<25

kg/m

2

<7

day

sN

RSt

able

donor

NR

ente

ralnutr

itio

n(5

0m

l/h)

asim

munonutr

itio

n

Yer

siz

etal

.[1

3]

2003

(rev

iew

of

oth

erst

udie

s)

NR

NR

NR

NR

No–m

inim

alva

sopre

ssor

requirem

ent

Na

<160*l

SDD

,sy

stem

ican

tibio

sis

CPR

,ca

rdio

pulm

onar

yre

susc

itat

ion;

NR,

not

report

ed;

SDD

,se

lect

ive

dec

onta

min

atio

nof

the

gut.

*m

mol/l

.

†m

g/d

l.

‡U

/l.

§Se

ries

of

single

-cen

tre

report

sre

gula

rly

updat

edw

ith

incl

usi

on

of

most

rece

nt

exper

ience

inin

test

inal

donor

sele

ctio

n.

Table 2. Donor and recipient data.

Variable Median (Range) or n (%)

Donor (n = 39)

Female/Male 24 (62)/15 (38)

Age (years) 21 (0.6–51)

Donor <18 years 17 (44)

Height (cm) 170 (78–195)

Weight (kg) 63 (11–85)

BMI (kg/m2) 21.2 (13.9–25.4)

ICU-Stay

(admission–cross-clamp h)

52.4 (20.9–242.3)

Brain death

certified–cross-clamp (h)

14.1 (7.6–33.7)

Cause of death (n = 20)

Trauma 17 (44)

Cerebrovascular accident 14 (36)

Ischaemic stroke 3 (8)

Anoxia 3 (8)

Meningitis (Neisseria) 1 (2)

Thrombosis of cerebral veins 1 (2)

Abdominal pathologies

Hip fracture + retroperitoneal

haematoma

1 (2)

VP-shunt for many years 1 (2)

Cardio-thoracic pathologies

Thoracic trauma

(inclusive lung contusion)

7 (18)

Aspiration/pneumonia 6 (15)

Pulmonary embolism 1 (2)

Asthma, recurrent pneumonias 1 (2)

Plaques in aorta ascendens 1 (2)

Cardiac arrest due to cardiac

reasons

2 (6)

Poor cardiac output for cerebral

reasons

7 (18)

Other pathologies (multiple counts)

Intra-cerebral vascular malformation 2 (5)

Epilepsia/hydrocephalus since birth 1 (2)

Trauma to peripheral extremities 7 (18)

Vertebral fracture 2 (5)

Anti-HBc and anti-HBs reactive 1 (2)

Nonreactive HIV- and

HCV-NAT (HRD-donor)

2 (5)

Arterial hypertension 3 (8)

Smoking 6 (15)

Alcohol abuse 1 (2)

Diabetes 0 (0)

Haemodynamic parameter

Mean arterial pressure

(mmHg, n = 39)

88 (65–115)

Diuresis (ml/kg BW/h, n = 39) 2.8 (1.2–12.3)

Central venous pressure

(mmHg, n = 25)

3 ()7 to 15)

Laboratory data (most recent)

Haemoglobin (g/dl, n = 39) 10.8 (7.6–15.5)

White blood cells (G/l, n = 39) 14.7 (6.2–47.7)

Platelets (G/l, n = 39) 156 (28–429)

Peak sodium last 24 h (mmol/l, n = 39) 150 (133–166)


ª 2012 The Authors


Most of the donors had normal values of liver enzymes

and serum sodium.

The donor–recipient weight ratio (DRWR) was 0.88

(0.52–1.71) and donor–recipient height ratio (DRHR)

was 0.96 (0.68–1.13).

The causes of death were traumatic brain injuries in 17

cases (44%) (7 isolated and 10 polytrauma), atraumatic

subarachnoid haemorrhage (SAH) in 9 (23%), spontane-

ous intra-cerebral bleeding (ICB) in 5 (13%), anoxic

brain damage due to cardiac arrest in 3 (8%), ischaemic

stroke in 3 (8%), Neisseria Meningitis in 1 (2%) and

thrombosis of cerebral vessels in 1 (2%).

The average time interval from ICU admission until

cross-clamping at the donor operation was 52 h (21–

243), i.e. 2 days (1–10).

At the time of hospital admission, 12 (31%) patients (4

head trauma, 5 SAH, 3 anoxia) were hemodynamically

unstable (defined as needing multiple transfusions and/or

high-dose vasopressors). The 3 head trauma patients

underwent an emergency craniectomy, which was associ-

ated with severe bleeding and cardio-circulatory compli-

cations due to extreme brain oedema. All of the 12

initially unstable donors recovered from their unstable

condition within 24 h.

Prehospital cardiac resuscitation was performed in 9

donors (see Table 3 for details): in 3 cases for primary

cardiac failure (duration: 15, 15 and 20 min each), in 5

cases secondary to SAH (duration: 1, 5, 10, 10 and

25 min each) and in 1 case secondary to poly-trauma

(3 min).

None of the 10 donors with a polytrauma experienced

identifiable blunt, direct or deceleration abdominal

trauma. These polytrauma donors included pedestrians,

motorcyclists and unrestrained motor vehicle passengers.

One donor experienced a hip fracture and retroperitoneal

haematoma.

Review of preprocurement donor management revealed

that donors received the following medications:

1 Vasopressors or inotropic agents: During the 12 h

prior to organ recovery, norepinephrine was administered

in 25 donors (76%) at an average dosage of 0.08 (0.02–

0.6) lg/kg/min and epinephrine in one paediatric donor

(5%) at a dosage of 0.14 lg/kg/min. Another paediatric

donor received dopamine (4 lg/kg/min) and dobutamine

(4 lg/kg/min). Due to neurocardiac injury after SAH one

donor received a combination of norepinephrine

(0.08 lg/kg/min) and dobutamine (2.08 lg/kg/min).

2 Antibiotics: Treatment was initiated in 22 cases (56%)

with therapeutic indication for pulmonary infection in 4,

meningitis in 1 and neurosurgery in 4.

3 Steroids: Hydrocortisone or prednisolone were admin-

istered in 27 patients (69%).

4 Insulin: Insulin was used for keeping the blood glucose

below 160 mg/dl in 15 cases (38%).

5 Desmopressin: Diabetes insipidus required administra-

tion of desmopressin in 26 cases (67%).

6 Transfusions: Following admission, blood products

were administered in 15 donors (39%) with an average of

5 (2–25) units of erythrocyte concentrate and 3 (0–25)

units of fresh frozen plasma.

7 Enteral nutrition: Feeding via the gastrointestinal tract

was initiated within 24 h after admission in all cases.

Selective intestinal decontamination was not performed.

Before organ recovery, all donors were stable: mean

arterial pressure (MAP) 88 mmHg (65–115), pH 7.40

Table 2. continued

Variable Median (Range) or n (%)

Most recent sodium (mmol/l, n = 39) 148 (119–166)

Creatinine (mmol/l, n = 39) 61.9 (15.9–97.2)

CK (U/l, n = 33) 340 (14–7874)

CKMB (U/l, n = 30) 37 (2–664)

Troponine (ng/ml, n = 25) 0.1 (<0.01–6.0)

ASAT (U/l, n = 38) 42.5 (9–653)

ALAT (U/l, n = 39) 23 (8–318)

yGT (U/l, n = 38) 18 (8–116)

Bilirubine (lmol/l, n = 39) 9.6 (1.5–34.0)

Amylase (U/l, n = 31) 55 (17–504)

Lipase (U/l, n = 36) 19.5 (4–270)

PT (measured as Quick in %, n = 39) 71 (44-114)

CRP (mg/l, n = 37) 99 (18–284)

PaO2/FIO2 (mmHg, n = 39) 452 (88–586)

pH (n = 38) 7.40 (7.19–7.64)

HCO3 (mmol/l, n = 37) 24.5 (20.0–33.0)

Base excess (mmol/l, n = 38) )0.05 ()5.70 to 8.60)

Anti-CMV reactive (n = 39) 17 (44)

Anti-EBV-VCA-IgG reactive (n = 36) 34 (94)

Anti-toxoplasmose reactive (n = 38) 15 (40)

Echocardiography (n = 36)

No pathology 23 (64)

Regional hypo-/akinesia 11 (31)

Plaques in aorta

ascendens/hypertrophy

2 (7)

Bronchoscopy (n = 32)

No pathology 18 (56)

Aspiration/blood/massive secretion 6 (19)

Inflammation 8 (25)

Recipient

Female/male 13 (33)/26 (67)

Age (years) 44.5 (3–59)

Recipients <18 years 4 (11)

Donor–recipient weight and size match

Donor/recipient weight ratio

(kg/kg, n = 24)

0.88 (0.52–1.72)

Donor/recipient size ratio

(cm/cm, n = 24)

0.96 (0.68–1.13)

Technical data

Median ischaemia time (h, n = 33) 6.2 h (3.1–12.1)


ª 2012 The Authors


(7.19–7.64), CVP was 7.0 mmHg ()3 to 15), temperature

36.2� C (35.1–38.8), heart rate 103.5 bpm (50–149) and

diuresis 2.8 ml/kg BW (1.2–12.3).

Different scores for organ donors based on graft type

were calculated:

1 The liver donor risk index (DRI) [15] was 1.38 (0.91–

2.93): 85% of all donors scored above the threshold of

1.0 for an ideal liver donor.

2 Expanded donor criteria (EDC): One donor (3%) met

3 liver specific EDC according to the guidelines of the

German Medical Association [16]; 4 patients met 2 crite-

rion (10%), 5 patients met 1 criterion (13%) and 29 none

(74%).

3 The pancreas PPASS-score [17] was 14 (10–19): 10%

of the donors scored above the threshold of 17 for an

ideal donor.

All procured intestinal grafts were transplanted: 20 IIT

and 19 MVT. In four cases (2 in IIT and 2 in MVT), the

intestinal graft included the ascending and transverse

colon.

Abdominal organs were perfused with UW-solution

(University of Wisconsin–Belzer Viaspan�; Bristol-Meyers

Squibb GmbH, Munich, Germany) in 10 donors [70 ml/

kgBW (42–200)] and with HTK-Solution (HTK Custodi-

ol�; Dr Franz Kohler Chemie, Alsbach-Haehnlein, Ger-

many) in 29 [143 ml/kgBW (92–204)].

The time frame from start of donor operation until

cross-clamping lasted 133 min (33–241), from cross-

clamping until removal of the intestinal graft 31 min (7–

68) and from start of donor operation until closure of

the body 230 min (149–330). Table 4 summarizes the

other organs recovered.

Intestinal graft survival rate at 30 days was

97.4% ± 2.5% and at 1-year, 73.0% ± 7.4% (median fol-

low up time 1.5 years. (0.04–4.2), (Fig. 1). Patient sur-

vival rates at 1 month and 1 year were 97.4% ± 2.5% and

75.6 ± 7.1% respectively.

Discussion

Until now, more than 2300 ITs have been performed

worldwide and mainly only large single-centre series have

Table 3. Data of the nine donors with prehospital cardiac arrest.

Age (years)/

Gender

Cause of

cardiac arrest

Duration of

CPR (min)

Time from

admission–

crossclamp (h)

Norepinephirine*

(lg/kg/min)

WBC*

G/l

Na+*

mmol/l

ASAT*

(U/l)

ALAT*

(U/l)

cGT*

(U/l)

Lipase*

(U/l)

Bili*

lmol/l

21 # AR,† 15 105.6 0.1 10.4 138 653 318 116 16 21

7 # AR,† 15 50.7 0.0 14.4 150 269 69 17 7 5

11 # Hypoxia,‡ 20 70.6 0.0 6.2 156 141 189 16 126 5.6

23 # Trauma,§ 3 57.8 0.036 12 149 111 59 20 20 26.7

36 $ SAH,§ 1 40.2 0.03 16.3 148 27 20 40 167 14

40 $ SAH,§ 5 57.2 0.062 17.6 142 30 27 24 39 3

31 $ SAH,– 10 24.9 0.3 15.0 141 108 146 31 13 13

17 # SAH,§ 25 72.2 0.0 14.7 141 28 32 31 7 10

24 # SAH,§ 10 62.6 0.083 14.8 155 60 15 17 11 12

AR, Arrhythmia; Bili, total serum bilirubine; CPR, cardiopulmonary resuscitation; Na+, serum sodium; SAH, subarachnoidal haemorrhage; WBC,

white blood cell count.

Hypoxia: Cardiac arrest due to hypoxia after strangulation; Trauma: cardiac arrest due to trauma complication.

#, Male.

$, Female.

*Most recent data before procurement.

†Heart not considered suitable for transplantation.

‡Heart not allocatable finally.

§Heart used for transplantation.

–Heart not used due to inferior pumping function intra-operatively.

Table 4. Other transplanted organs from the same donors.

Organ Transplantations Reason for grafts not transplanted/used

Heart 26 (66.7%) n = 13: 2 arrhythmia, 9 poor function,

1 coronary heart disease, 1 no

permission, 1 others

Lung 29* (69.7%) n = 12: 3 trauma, 5 aspiration/

pneumonia, 1 asthma, 1 size mismatch,

2 others

Liver 45† (100%) –

Pancreas 31 (79.5%) n = 7: 4 SMA-SMV anatomy/lesion,

1 oedema, 3 others

Kidney 77 (98.7%) n = 1:1 atherosclerotic plaque in a. renalis

The percentage in column Transplantations refers to conversion rate

of possible grafts to be transplanted.

*25 double-lung and 4 single-lung grafts.

†6 grafts used for 12 split liver transplantations, in 3 cases, a split was

intended.


ª 2012 The Authors


been reported [4,9,18–21]. Interestingly, based on our

review of the literature [5–13], no clear data about intes-

tinal donor criteria (Table 1) with exception of donor age

(<50 years) and donor–recipient size match (donor

should be smaller than recipient) have been reported.

This ambiguity and lack of guidance cause confusion for

those involved in evaluating organ donors.

We therefore set out to provide the medical commu-

nity, ICU staff, coordinators, OPOs and transplant sur-

geons with simple guidelines for intestinal donor

‘inclusion-criteria’. To this end, we discuss the medical

literature in the context of our intestinal donation experi-

ence in Germany during the past 5 years.

A detailed analysis of each key parameter follows:

Donor–recipient size match

The lack of intra-abdominal space represents a major

problem for IIT and MVT, as the recipient’s abdominal

cavity is often small and retracted. Many authors

addressed this issue [6,7,9,21–23], generally concluding

that grafts from donors 25–50% smaller than the recipi-

ent are preferred without specific recommendations about

height or weight. We postulated that the correctly mea-

sured donor’s height and weight [24] may be useful this

context. As the calculated DRWR and DRHR from our

donor–recipient pairs were 0.88 (0.52–1.71) and 0.96

(0.68–1.13) respectively, most donors were approximately

the same size as the recipient. However, as demonstrated

by several authors, size reduction or adaptation of the

graft may be possible to overcome the burden of donor–

recipient size mismatch [7,25,26].

Therefore, we do not consider donor size mismatch to

be an absolute exclusion criterion and cannot recommend

a cut off for donor height and weight.

High BMI may correlate with high fat content in the

mesenteric root causing obstacles during the implantation

of the graft; however, neither the literature nor our data

suggest a clear cut-off for donor BMI. On the basis of

our personal experience, we suggest to consider IT-dona-

tion in donors with BMI <28.

ICU stay

The median ICU stay in our series was 2 days [1–10].

This was similar to the reported data in the literature

[8–13,22,27]. There is consensus that intensive donor

therapy improves the quality of organs [28].

Notwithstanding, an ICU-stay longer than 1 week

should not exclude intestinal donation [11], if enteral

nutrition is started as soon as possible after admission to

the ICU, as recommended by guidelines for enteral nutri-

tion [29]. This avoids disruption of the mucosa barrier

and progression to luminal ileus, as well as stabilizes

colon function and its flora if antibiotics are not added

inappropriately [30]. Any available standard enteral nutri-

tion has been shown to have a benefit over nothing [29],

as long as it is not contaminated by microbes. Even

100%*1*290%

80%

*10*9

*7*8

*5*6

*3*4

50%

60%

70%

*1 Dead (multi organ failure)*2 Dead (peritonitis)*3 Dead (impaired graft function)

*12*11

Gra

ft fu

ctio

n ra

te

30%

40% *5 Dead (sepsis)*6 Rejection (necorsis, alive)

*4 Dead (GVHD -> fungal-sepsis)

*7 Dead (perforation -> infection)

10%

20%*8 Dead (PTLD)*9 Dead (PTLD, mycotic aneurysm)*10 Dead (aspergillus-sepsis)*11 Dead (incompliance, sepsis)

0 1 2 3

0%*12 Dead (sudden death at home)

Years after intestinal transplantation

Figure 1 Intestinal graft survival rates from deceased donors procured in Germany between January 2006 and December 2011. The cause of

graft loss is inserted in graph (marked with*). During the first year, they were in nine cases secondary to multiorgan failure, peritonitis, graft-ver-

sus-host disease (GVHD), sepsis due to various pathogens, rejection, PTLD and ischaemia due to ruptured mycotic arterial aneurysm as well as in

one case without confirmed reason of death, but known impaired graft function.


ª 2012 The Authors


50 ml/h of unsweetened tea may preserve intestinal integ-

rity in short-term.

Cause of death

The cause of the donor’s death, in and of itself, does not

represent an exclusion criterion a priori in our experience

as also echoed by others [11]. Notwithstanding, in the

case of a post-traumatic death, the mechanism of trauma

and injury represents a major role in donor selection for

intestinal donation: a direct abdominal trauma (blunt as

well as open), a severe deceleration trauma with conse-

quent potential laceration of the mesenteric root and

bowel and cases of pancreatitis should represent contrain-

dications to intestinal donation.

Other traumatic extra-abdominal lesions (i.e. thorax

and extremities) should not represent a contraindication.

Vasopressors

In our series, 31% of the donors were haemodynamically

unstable right after hospital admission, but subsequently

recovered! Reasons for hypotension included polytrauma

injuries, poor cardiac output after SAH/ICB and recovery

following prehospital cardiac arrest with resuscitation.

Initial hemodynamic instability was treated with vaso-

pressors and inotropics, (e.g. norepinephrine >0.1 lg/kg/

min supplemented by dobutamine >10 lg/kg/min), as

well as transfusions as necessary until proper circulation

was achieved. While there is concern that high doses of

vasoactive medications may damage organs through vis-

ceral vasoconstriction, all unstable donors in our series

recovered hemodynamically and subsequently their organ

function recovered as well. In conclusion, short-term use

of a high dosage of vasopressors in donors unstable

upon hospital admission does not exclude intestinal

donation.

In a similar way, Audibert and Mertens recommended

the treatment of unphysiologic conditions in any patient

to preserve the option of organ/heart-donation in patients

without any chance of survival [31]. Their example is the

treatment of complications of brain stem coning during

the period of autonomic storm (e.g. antihypertensive

therapy by esmolol or urapidil) as well as the poor car-

diac output and hypotension right afterwards (e.g. by

norepinephrine and dobutamine) for potential cardiac

donors.

In our study population, intestinal donors with a

poor cardiac output due to SAH-associated heart insuf-

ficiency required higher doses of catecholamines. The

question of which catecholamine dosage and which

agents are detrimental in organ procurement remains

unanswered.

Cardiac arrest and cardio-pulmonary resuscitation

Cardiac arrest should not automatically preclude subse-

quent donation of an intestinal graft. To this end, Mat-

sumoto et al. observed no inferior outcome in IIT and

MVT when comparing grafts retrieved from donors with

and without cardiac arrest [11]. Mean duration of cardiac

arrest and subsequent cardio-pulmonary-resucitation

(CPR) was 19.3 ± 12.7 min (range 1–52 min) with a time

interval lasting from admission until cross clamp of

115 ± 61.7 h in a young donor population (7.66 ±

12.57 years). Compared with donors without CPR, no

differences in terminal laboratory values as well as out-

come parameters of the recipients were observed [11].

These results were confirmed by our data, with no differ-

ences in graft function. In our series, the donors with

CPR were older when compared with the population of

Matsumoto et al. (median 23 years, range 7–40 years),

the duration of CPR was shorter (median 10 min, range

1–25 min) as was the time from admission until cross

clamp (median 58 h, range 25–106 h), while terminal lab-

oratory data had a wide variation (see Table 3).

In our series, the brain–heart connection related to car-

diac failure after severe SAH [32] was responsible for car-

diac arrest in all donors with SAH needing prehospital

CPR. Echocardiography in these donors showed regional

wall-motion-abnormalities or poor left ventricular output

associated with the SAH, known as stress cardiomyopathy

[33]. This entity and the potential for full hemodynamic

recovery must be considered during donor selection.

Our data are in direct contrast to previous reports,

which state that intestinal donors should not have any

significant history of cardiac arrest or hemodynamic

instability [6,7,12,21–23].

Age

The literature suggests that ideal intestinal donor should

be younger than 50 years [5,6,8–13,27,34]. Although

donors older than 50 years have been used successfully

[9,34], our results were similar to those reported in the

literature with most donors being younger than 18 years

and only one over 50 years of age.

Laboratory values

Abnormal laboratory data require a case-by-case decision.

Sodium level (and its trend over time) represented the

most important parameter influencing the acceptance of

intestinal grafts. In our series, median peak sodium was

150 mmol/l and median sodium before procurement was

148 mmol/l. The sodium should be kept within normal

range [13,28,34,35] for avoiding adverse events.


ª 2012 The Authors


In the series investigated, the last liver enzyme values

showed a wide range, even higher than in other studies

[11].

After periods with a risk of intestinal ischaemia, it is

important to know the trend of liver enzymes, bilirubin

and creatinine. Decreasing values back towards normal

range indicate a recovery, while increasing values need a

careful evaluation.

Liver enzymes (ASAT, ALAT) twice above the reference

range as well as creatinine and bilirubin in the reference

range following CPR (and presumed significant intestinal

ischaemia) had no impact on the outcome of IIT or

MVT according to the study of Matsumoto et al. [11].

Inflammation markers were elevated in the study popu-

lation, which was a frequent observation in donors due to

brain tissue destruction and the SIRS associated with it

[14,35]. Lactate and ph were not explicitly documented in

most of studies, but we assume that these parameters

were usually within normal range.

Medications

Diabetes insipidus should be treated by application of

antidiuretic hormone [35].

Insulin therapy was required in many donors due to

the target value of keeping the blood glucose below 160–

200 mg/dl. Therefore, insulin use in donors simply

reflected the quality of intensive care provided to the

donor. Insulin application is also part of successful proto-

cols of hormonal resuscitation in organ donors [28,36].

Treatment with steroids has a catecholamine-sparing

effect, decreases the complications of the brain death-

induced SIRS [35,37], offers a beneficial side effect of

immune-modulation and an improvement of lung func-

tion [35]. Steroids are part of protocols of hormonal

resuscitation in organ donors [28,36].

Donor risk scores

The application of different donor risk scores for predict-

ing organ quality [15–17,38] appeared at first glance to

be helpful. But, after a critical review, we concluded that

their use would have merely resulted in the inappropriate

exclusion of grafts, which were transplanted successfully,

e.g. DRI for the liver was out of the ideal range in 82%

of the cases.

Blood group

Previous publications have stated that identical AB0

blood group is preferred [6,21]. This limits the pool of

available donors for a recipient. In our cohort, one AB0

compatible IIT- and one MVT were performed without

impact on outcome. All others were AB0 identical.

Preservation solution

In a recent review about small bowel preservation for IT,

Roskott et al. reported that UW solution is suboptimal

for the intestinal graft despite good results for other

organs and that extracellular solutions like HTK should

be preferred [39].

In our series, 10 grafts had been preserved with UW-

solution and 29 with HTK -solution. All grafts had

primary function and an ischaemia time below 12 h. No

differences in 1-year graft function rates were detected.

The same results were obtained in a larger group investi-

gated by Mangus et al. [27] with 22 grafts preserved in

UW and 37 in HTK. In MVT-grafts, they did not observe

complications related to the pancreas when comparing

the solutions. From our data, it can be concluded that

HTK was equivalent to UW for preservation of an intesti-

nal graft for ischaemia times below 12 h. In contrast,

Abu-Elmagd et al. [4] reported additional pancreatic

complications in MVT grafts perfused with HTK com-

pared with UW. HTK will be suitable for all intestinal

grafts perhaps except for MVT grafts containing the pan-

creas due to the elevated risk of pancreatic complications.

Another risk factor to be taken into serious consider-

ation is the use of an inappropriate flush volume with

any solution if it is not weight-adjusted according to the

manufacturer’s instructions.

Other factors

The procurement of an IIT- or a MVT-graft requires the

preservation of structures not routinely considered

important in nonintestinal donors. This is especially true

when including the colon with the intestinal graft or

when the intestinal recipient has other individual ana-

tomic needs to consider. Therefore, the surgeon experi-

enced in intestinal procurement (usually coming from the

transplant centre accepting the intestinal graft) must be

present from the start of donor operation until the end.

Analysis of outcome

All transplanted intestinal grafts, but one in our series,

were functioning after 30 days. In fact, one recipient died

within 30 days not due to graft-related complications. A

1-year graft function rate of 73.0 ± 7.4% is comparable to

the results reported in the cited literature. Survival rate

and the reasons for graft failures within the first years are

shown in Fig. 1. No correlation between the reason for


ª 2012 The Authors


graft loss and donor variables could be identified beyond

the factors discussed.

Conclusion

While our study focuses on the 39 German donors from

whom intestinal grafts were successfully transplanted, we

believe that the number of potential donor candidates

who were not utilized is even more relevant. Although

difficult to quantify, a review of German data [40] sug-

gests that many potentially suitable intestinal donors are

turned down for unclear reasons: for example, of the

6426 realized donors between 2006 and 2010, 0.5% intes-

tinal grafts were used for transplantation (n = 33) com-

pared to 10.3% of the pancreas and 77.0% of the liver

grafts. It is impossible to quantify the basis for declining

a specific potential donor, but personal communications

with colleagues reveal that many donors are refused sim-

ply because of an uncertainty about their suitability. We

acknowledge that our study group is small and therefore

the power of statistical analysis is limited, but we have no

control over past utilization of intestinal donors. This

should not be an obstacle for describing ‘inclusion- crite-

ria’ to be used during donor evaluation. Only by seeking

to provide clarity to the issue, we can expand the intesti-

nal donor pool. As all grafts had initial function, someone

might argue that the selection of donors had been conser-

vative. Still the range of donor data was beyond the scope

usually communicated without severe adverse events/reac-

tions reported. Unfortunately, this experience provides

no risk stratification into good or bad donor characteris-

tics, but at least we know when it is safe to consider

donation of IT-graft.

On the basis of collected data, we suggest following

inclusion criteria for donation of IT grafts (see also

Table 5): donor age 0–50 years, ICU-stay <1 week, no

blunt abdominal trauma, most recent Sodium

<155 mmol/l, no severe ongoing transfusion require-

ments, standard donor therapy including enteral nutrition

and a compatible donor–recipient size match. HTK-solu-

tion appeared to be safe for organ preservation if ischae-

mia time was kept below 12 h.

We believe that any donor meeting these criteria

should be considered potentially suitable and no other

parameters should be used as an excuse for excluding

intestinal grafts without seeking input from intestinal

transplant centres.

Authorship

CLFF: designed research, collected data, analysed data

and wrote the manuscript. AK: contributed important

data for research design. RS: contributed important

data for research design and wrote the manuscript. FS:

contributed important data for research design, col-

lected data, and analysed data. JP and AP: contributed

important data for research design and collected data.

WS: contributed important data for research design.

SN: contributed important data for research design,

designed research, analysed data and wrote the manu-

script.

Funding

The authors have declared no funding.

Acknowledgement

The authors want to thank all coordinators and donor

hospitals for their huge and essential contribution in real-

izing IT as well as recipient centres in providing follow-

up information on graft function and critical remarks

(Innsbruck, Groningen, Leuven, Berlin, Frankfurt, Jena,

Muenster, Munich, Tuebingen, Eurotransplant).

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Table 5. Currently proposed standard inclusion criteria for intestinal

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Donor data Range in an ideal donor

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ª 2012 The Authors


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Organ donation: when should we consider intestinal donation